Mitochondrial oxidative phosphorylation system assembly in man: recent achievements

The human oxidative phosphorylation system consists of five multi-subunit complexes of which the individual subunits, with the exception of complex II, are encoded either by mitochondrial or nuclear DNA. Consequently, a deficient enzyme activity of one or more of the complexes can be caused by mitochondrial or nuclear DNA mutations. In the past 5 years numerous mutations have been found in structural nuclear oxidative phosphorylation system genes. However, in a substantial number of patients with oxidative phosphorylation system complex deficiencies, despite extensive investigations, no mutations in the mitochondrial DNA or the structural nuclear genes have been found. Genetic defects in such patients are therefore suspected at the transcriptional, translational, post-translational level or in gene products involved in the assembly of the oxidative phosphorylation system. The latter is a complicated process, as the proteins encoded by the two genomes have to be brought together in a proper stoichiometric way to form five functional complexes. In the past year substantial progress in the knowledge of the human oxidative phosphorylation assembly process has been made. Several human assembly genes have been identified, and mutations in these genes responsible for human oxidative phosphorylation system complex-related diseases have been found. In this review, we summarize our current knowledge about human oxidative phosphorylation system assembly genes in health and disease.